1,2-Dichloroethane → (s)-7-Chloro-2-neopentyl-4-(2-oxo-2-(4-(5-oxo-4,5-dihydro-1h-pyrrolo[3,2-b]pyridin-6-yl)piperidin-1-yl)ethyl)-1,2,4,5-tetrahydroazepino[3,4-e]indol-3(8h)-one

HRID 2378995노트

반응식

HRID 2378995 반응식
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:12](=[O:13])[NH:11][C:10]3[CH:14]=[CH:15][NH:16][C:9]=3[CH:8]=2)[CH2:3][CH2:2]1.[Cl:17][C:18]1[CH:19]=[C:20]2[CH2:31][C@@H:30]([CH2:32][C:33](O)=[O:34])[C:29](=[O:36])[N:28]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:27][C:21]2=[C:22]2[C:26]=1[NH:25][CH:24]=[CH:23]2.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C>CN(C=O)C>[Cl:17][C:18]1[CH:19]=[C:20]2[CH2:31][C@@H:30]([CH2:32][C:33](=[O:34])[N:1]3[CH2:2][CH2:3][CH:4]([C:7]4[C:12](=[O:13])[NH:11][C:10]5[CH:14]=[CH:15][NH:16][C:9]=5[CH:8]=4)[CH2:5][CH2:6]3)[C:29](=[O:36])[N:28]([CH2:37][C:38]([CH3:41])([CH3:40])[CH3:39])[CH2:27][C:21]2=[C:22]2[C:26]=1[NH:25][CH:24]=[CH:23]2

참가 물질

7

반응물 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 590063956-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5(4H)-oneHCID 68892930(S)-2-(7-chloro-2-neopentyl-3-oxo-1,2,3,4,5,8-hexahydroazepino[3,4-e]indol-4-yl)acetic acid

생성물 1

HCID 23658028(s)-7-Chloro-2-neopentyl-4-(2-oxo-2-(4-(5-oxo-4,5-dihydro-1h-pyrrolo[3,2-b]pyridin-6-yl)piperidin-1-yl)ethyl)-1,2,4,5-tetrahydroazepino[3,4-e]indol-3(8h)-one수율 16.2%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

To 6-(piperidin-4-yl)-1H-pyrrolo[3,2-b]pyridin-5(4H)-one (60.0 mg, 0.276 mmol) was added (S)-2-(7-chloro-2-neopentyl-3-oxo-1,2,3,4,5,8-hexahydroazepino[3,4-e]indol-4-yl) acetic acid (100 mg, 0.276 mmol), EDC (58.3 mg, 0.304 mmol), HOBT (41.0 mg, 0.304 mmol), DMF (2.0 ml) at rt, followed by diisopropylethylamine (0.192 ml, 1.10 mmol). The resulting mixture was stirred at rt over night, partial of the solvent was removed under N2, and the residue was purified on reverse phase PrepHPLC to afford the expected products(25.2 mg, 16%), (S)-7-chloro-2-neopentyl-4-(2-oxo-2-(4-(5-oxo-4,5-dihydro-1H-pyrrolo [3,2-b]pyridin-6-yl)piperidin-1-yl)ethyl)-1,2,4,5-tetrahydroazepino [3,4-e]indol-3 (8H)-one, as a tan solid. 1H-NMR (400 MHz, MeOD) d 0.79 (d, J=5.29 Hz, 11H) 1.52-1.62 (m, 1H) 1.81 (s, 1H) 2.38-2.49 (m, 1H) 2.75 (s, 1H) 3.01 (d, J=13.35 Hz, 1H) 3.09-3.21 (m, 4H) 3.66 (d, J=13.85 Hz, 1H) 3.96 (s, 3H) 3.99-4.06 (m, 1H) 4.24 (s, 1H) 4.65 (d, J=17.37 Hz, 2H) 5.46-5.55 (m, 1H) 6.27 (dd, J=5.29, 3.02 Hz, 1H) 7.22 (s, 1H) 7.36 (dd, J=7.81, 3.02 Hz, 1H) 8.24 (s, 1H); Mass spec 562.48 (MH+) calc for C31H36ClN5O3 561.25.

후처리

  1. customwas removed under N2
  2. customthe residue was purified on reverse phase PrepHPLC

출처 및 근거

ORD 기록
ord-374b439b8d5b4a9cbdb4b0614785c14d
출처 데이터셋
uspto-grants-2008_12
특허 번호
US07470680B2

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